Key result
High-sensitivity cardiac troponin interpretation requires clinical context across 4 domains rather than algorithms alone.
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Why the study?
High-sensitivity cardiac troponin assays readily detect myocardial injury across diverse cardiac and systemic diseases, creating a central clinical challenge of accurately classifying the injury. Misclassification is common, leading to both the overdiagnosis of secondary myocardial infarction in nonischemic injury and the routine dismissal of high-risk chronic myocardial injury once infarction is excluded.
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“Detection is now easy, but classification is not," Spanos and Januzzi conclude. "The limiting step in troponin interpretation is no longer analytical sensitivity but diagnostic discipline and approach.”
This narrative review provides bedside guidance for the context-aware clinical interpretation of high-sensitivity cardiac troponin assays to accurately classify myocardial injury and prevent the misdiagnosis of secondary or chronic myocardial injury.
High-sensitivity cardiac troponin (hs-cTn) assays have solved the problem of detecting myocardial injury and, in doing so, created the problem of classifying it. Abnormal troponin concentrations are now known to be common across a wide spectrum of cardiac and systemic disease, and the central challenge of contemporary practice is no longer whether myocardial injury can be detected, but whether it can be correctly classified. Misclassification occurs in both directions and with real consequence: nonischemic myocardial injury is frequently mislabeled as secondary myocardial infarction (MI), contributing to the overdiagnosis of MI, and chronic myocardial injury, which carries a risk of subsequent MI or cardiovascular death approaching that of primary MI, is routinely dismissed once infarction has been excluded. This narrative review argues that accurate classification cannot be delegated to an algorithm and instead requires integrated, context-aware interpretation grounded in 4 domains: 1) the analytical and biological properties of hs-cTnI and hs-cTnT, including assay-specific and sex-specific thresholds, clearance kinetics, and sources of analytical interference and false-positive results; 2) the capabilities and limitations of guideline-endorsed serial testing, including the European Society of Cardiology 0/1h and 0/2h algorithms, point-of-care platforms, and artificial intelligence-based decision support; 3) rigorous application of the Fifth Universal Definition of Myocardial Infarction, in particular the distinctions between myocardial injury, necrosis, and infarction, and between diagnosis and risk stratification; and 4) recognition of the non-acute coronary syndrome conditions-chronic kidney disease, heart failure, sepsis, tachyarrhythmias, pulmonary embolism, takotsubo syndrome, and others-in which troponin elevation is expected rather than anomalous. We provide explicit bedside guidance for the situations that clinicians find most difficult, including suspected secondary MI, the observe zone, and troponin elevation without a dynamic pattern. Finally, we review emerging understanding of troponin biology, clearance, proteolysis and fragmentation, macrotroponin, antitroponin autoantibodies, and extracellular vesicle-associated troponin, which may eventually allow the assay itself to carry more of the interpretive burden. Until then, that burden rests with the clinician.
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Spanos et al. (2026) conducted a review in Myocardial injury and myocardial infarction. High-sensitivity cardiac troponin (hs-cTn) assay interpretation was evaluated. High-sensitivity cardiac troponin classification requires context-aware interpretation across 4 domains rather than delegating diagnosis to an algorithm alone.
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